Trimodal therapy offers QALY gain vs. cystectomy

A bladder-sparing approach for the treatment of muscle-invasive bladder cancer increases quality-adjusted life years compared with radical cystectomy in appropriately selected patients.

A bladder-sparing approach for the treatment of muscle-invasive bladder cancer (MIBC) increases quality-adjusted life years (QALY) compared with radical cystectomy in appropriately selected patients.

A Markov model simulating lifetime outcomes demonstrated an incremental gain in effectiveness of more than 1 QALY with trimodal therapy compared with radical cystectomy in patients with American Joint Committee on Cancer clinical stage T2-T4aN0M0 MIBC, Massachusetts General Hospital researchers found.

Trimodal therapy refers to maximal transurethral resection of the bladder tumor followed by concurrent chemotherapy and radiation, thereby sparing the bladder.

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“These results, while not the level III evidence that a large randomized trial would provide, suggest that perhaps there is a quality of life benefit with preservation of the native bladder, which is the whole goal of trimodality therapy. If anything, this supports further research into the quality of life of these two treatment approaches,” said Trevor Joseph Royce, MD, chief resident in radiation oncology at Massachusetts General Hospital, Boston, working with Jason Efstathiou, MD, and colleagues.

Data are limited comparing trimodal therapy with radical cystectomy. As presented at the Genitourinary Cancers Symposium in San Francisco, lifetime outcomes were simulated for 67-year-old patients after definitive treatment using either trimodal therapy or radical cystectomy with or without neoadjuvant chemotherapy, with the primary endpoint being QALYs.

“Both treatment approaches are recommended by guidelines for definitive treatment of MIBC, and there is no randomized evidence comparing the two. We tried to at least generate hypotheses with alternative research approaches that are not randomized controlled trials, and one example is the modeling study we performed. We looked at the quality of life component under the general assumption that they have about the same survival,” Dr. Royce said.

The model found trimodal therapy to be associated with 8.37 QALYs compared with 7.24 QALYs for radical cystectomy, representing a gain of 1.13 QALY with trimodal therapy. The QALY advantage to trimodal therapy is mainly a reflection of a quality of life difference between the two strategies, as demonstrated in one-way sensitivity analyses, he said.

Next:Benefit persists in low-risk cohortBenefit persists in low-risk cohort

The gain in QALY with trimodal therapy persisted (8.37 vs. 7.76 QALYs, for a difference of 0.61 QALYs) when the radical cystectomy strategy was limited to a more favorable low-risk MIBC cohort, defined as clinical T2 disease without hydroureteronephrosis, lymphovascular invasion, or micropapillary disease. Trimodal therapy was more effective than radical cystectomy irrespective of the radical cystectomy utility value; testing the 95% confidence interval of the radical cystectomy utility demonstrated an incremental gain with trimodal therapy of 0.01 to 4.77 QALYs.

Probabilistic sensitivity analysis demonstrated that trimodal therapy was more effective than radical cystectomy for 75% of model iterations.

“A major limitation of a modeling study is that the modeling is only as good as the data inputs you can provide for the model,” Dr. Royce said. “So that’s a caveat.”

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Finding quality of life differences between the approaches would be difficult with a randomized trial, although it had been attempted in the SPARE (Selective Bladder Preservation Versus Radical Cystectomy) trial. The SPARE trial closed as patient accrual proved difficult.

“This represents a gap in the literature, and one way to try to address that gap is by doing alternative studies such as we did,” Dr. Royce said.

The finding supports consideration of trimodal therapy in a multidisciplinary setting of appropriate candidates, such as those with solitary tumors (<5 cm), minimal or no hydronephrosis, good bladder function, and no multifocal carcinoma in situ, he said.

One study co-authors is a consultant/adviser to Olympus, another has received research funding from Medical Imaging and Technology Alliance for unrelated work, and Dr. Efstathiou is a consultant/adviser for Bayer, Genentech, and Medivation/Astellas.



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